title: Randomized phase II study of vandetanib alone or with paclitaxel and carboplatin as first-line treatment for advanced non-small-cell lung cancer.
abstract: OBJECTIVE
  Vandetanib is a once-daily, oral inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling. The antitumor activity of vandetanib monotherapy or vandetanib with paclitaxel and carboplatin (VPC) was compared with paclitaxel and carboplatin (PC) in previously untreated patients with non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  All NSCLC histologies and previously treated CNS metastases were permitted in this partially blinded, placebo-controlled, randomized phase II study. Patients were randomly assigned 2:1:1 to receive vandetanib, VPC, or PC. Progression-free survival (PFS) was the primary end point, and the study was powered to detect a reduced risk of progression with VPC versus PC (hazard ratio = 0.70; one-sided P < .2) and to demonstrate noninferiority for vandetanib versus PC. Overall survival was a secondary assessment.
  
  
  RESULTS
  The risk of progression was reduced for patients receiving VPC (n = 56) versus PC (n = 52; hazard ratio = 0.76, one-sided P = .098); median PFS was 24 weeks (VPC) and 23 weeks (PC). The vandetanib monotherapy arm (n = 73) was discontinued after a planned interim PFS analysis met the criterion for discontinuation (hazard ratio > 1.33 v PC). Overall survival was not significantly different between patients receiving VPC or PC. Rash, diarrhea, and hypertension were common adverse events; no pulmonary or CNS hemorrhage events required intervention.
  
  
  CONCLUSIONS
  VPC could be safely administered to patients with NSCLC, including those with squamous cell histology and treated brain metastases. Compared with the PC control arm, patients receiving VPC had longer PFS, meeting the prespecified study end point, whereas those receiving vandetanib monotherapy had shorter PFS.
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: John V
authors.initials: JV
authors.lastname: Heymach
authors.forename: Luis
authors.initials: L
authors.lastname: Paz-Ares
authors.forename: Filippo
authors.initials: F
authors.lastname: De Braud
authors.forename: Martin
authors.initials: M
authors.lastname: Sebastian
authors.forename: David J
authors.initials: DJ
authors.lastname: Stewart
authors.forename: Wilfried E E
authors.initials: WE
authors.lastname: Eberhardt
authors.forename: Anantbhushan A
authors.initials: AA
authors.lastname: Ranade
authors.forename: Graham
authors.initials: G
authors.lastname: Cohen
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Trigo
authors.forename: Alan B
authors.initials: AB
authors.lastname: Sandler
authors.forename: Philip D
authors.initials: PD
authors.lastname: Bonomi
authors.forename: Roy S
authors.initials: RS
authors.lastname: Herbst
authors.forename: Annetta D
authors.initials: AD
authors.lastname: Krebs
authors.forename: James
authors.initials: J
authors.lastname: Vasselli
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Johnson
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D010880:Piperidines; D011799:Quinazolines; D042461:Vascular Endothelial Growth Factor A; D016190:Carboplatin; D017239:Paclitaxel; C452423:vandetanib